一例17α-羟化酶缺乏症患者的临床及分子遗传学分析

Clinical and genetic analysis of a patient with 17α-hydroxylase/17,20-lyase deficiency

目的研究一例17α-羟化酶缺乏症患者的临床特征和分子遗传学机制。方法先证者社会性别为女性,因未避孕未孕就诊,实验室检查示染色体核型为46,XX。采集先证者及其家系成员的外周血样抽提基因组DNA,采用PCR扩增CYP17A1基因编码区8个外显子和DNA直接测序的方法对该家系成员进行遗传变异分析。结果Sanger测序分析发现先证者CYP17A1基因第8外显子存在c.1486C>T(p.Arg496Cys)纯合变异,导致其编码蛋白第496位精氨酸变异为半胱氨酸,经测序验证,先证者父母及其弟妹均为c.1486C>T杂合变异携带者。结论CYP17A1基因c.1486C>T纯合变异是导致该患者发生17α-羟化酶缺乏症的致病变异。本研究的结果能为其家系成员提供准确的遗传咨询与产前诊断。

Objective To explore the clinical and genetic characteristics of a patient with 17-hydroxylase/17,20-lyase deficiency.Methods The patient was infertile without contraception.Laboratory examination showed her chromosomal karyotype to be 46,XX.DNA sequencing was performed to detect variants of CYP17A1 gene in the patient and her family members.Results Sanger sequencing revealed that the patient has carried homozygous variant c.1486C>T in the exon 8 of the CYP17A1 gene,which resulted in substitution of arginine by cysteine(p.Arg496Cys).Her family members were all heterozygotes for the same variant.Conclusion Homozygous variant of the CYP17A1 gene c.1486C>T probably underlay the 17-hydroxylase deficiency in this patient.Above finding has enabled accurate genetic counseling and prenatal diagnosis for her family.